Reconstitution and Administration

Ticarcillin disodium and clavulanate potassium is administered by IV infusion over 30 minutes.

IV Infusion

Vials of ticarcillin disodium and clavulanate potassium labeled as containing a combined potency of 3.1 g of the drugs are reconstituted by adding approximately 13 mL of sterile water for injection or sodium chloride injection to provide a solution containing approximately 200 mg of ticarcillin per mL and 6.7 mg of clavulanic acid per mL. The vial should be shaken until the drug is dissolved. For intermittent IV infusion, reconstituted solutions of ticarcillin disodium and clavulanate potassium containing approximately 200 mg of ticarcillin per mL should be further diluted to a concentration of 10-100 mg/mL in a compatible IV solution.

Alternatively, ADD-Vantage® vials of the drug can be reconstituted according to the manufacturer’s directions. Pharmacy bulk packages labeled as containing a combined potency of 31 g of the drug are reconstituted by adding 76 mL of sterile water for injection or sodium chloride injection to the vial to provide a solution containing approximately 300 and 10 mg/mL of ticarcillin and clavulanic acid, respectively; for ease of reconstitution, the diluent may be added in 2 portions. Pharmacy bulk packages of the drug are not intended for direct IV infusion; prior to administration, solutions reconstituted in the pharmacy bulk package must be further diluted with a compatible IV infusion solution to a concentration of 10-100 mg/mL of ticarcillin.

Thawed solutions of the commercially available ticarcillin disodium and clavulanate potassium frozen injections should be administered only by IV infusion. The commercially available frozen ticarcillin disodium and clavulanate potassium injections should be thawed at room temperature (22°C) or in a refrigerator (4°C); the frozen injection should not be thawed by warming them in a water bath or by exposure to microwave radiation.

A precipitate may form while the commercially available injection in dextrose is frozen; however, this usually will dissolve with little or no agitation upon reaching room temperature. After thawing at room temperature, the containers should be checked for minute leaks by firmly squeezing the bag. The injection should be discarded if the container seal or outlet ports are not intact or leaks are found or if the solution is cloudy, discolored, or contains a precipitate. Additives should not be introduced into the injection container. The injections should not be used in series connections with other plastic containers, since such use could result in air embolism from residual air being drawn from the primary container before administration of fluid from the secondary container is complete.

Intermittent IV infusions of the drug should be infused over 30 minutes. Intermittent IV infusions of the drug may be administered directly into a vein or via a Y-type administration set. When a Y-type administration set is used, other IV solutions flowing through a common administration tubing or site should be discontinued while ticarcillin disodium and clavulanate potassium is being infused. If an aminoglycoside or other anti-infective agent is administered concomitantly with ticarcillin disodium and clavulanate potassium, the drugs should be administered separately. Reconstituted, diluted, and thawed solutions of ticarcillin disodium and clavulanate potassium should be inspected visually for particulate matter and discoloration prior to administration.

Dosage

Dosage of ticarcillin disodium and clavulanate potassium is expressed in terms of g of ticarcillin plus g of clavulanic acid (i.e., g of “Timentin®”) or in terms of the ticarcillin content of the fixed-ratio combination. Although commercially available ticarcillin disodium and clavulanate potassium contains ticarcillin as the disodium salt and clavulanic acid as the potassium salt, potency of ticarcillin disodium is expressed in terms of ticarcillin and potency of clavulanate potassium is expressed in terms of clavulanic acid.

Adult Dosage

The usual dosage of ticarcillin disodium and clavulanate potassium for the treatment of systemic or urinary tract infections in adults weighing 60 kg or more is 3.1 g of the 30:1 fixed-ratio combination (3 g of ticarcillin and 100 mg of clavulanic acid) every 4-6 hours.

Some clinicians suggest that for the treatment of urinary tract infections, 3.1 g of the 30:1 fixed-ratio combination every 6-8 hours may be adequate in these adults. For the treatment of gynecologic infections (e.g., endometritis) in adults, the usual dosage of the 30:1 fixed-ratio combination (3 g of ticarcillin and 100 mg of clavulanic acid) is 200 mg of ticarcillin per kg daily given in divided doses every 4-6 hours for moderate infections and 300 mg of ticarcillin per kg daily given in divided doses every 4 hours for severe infections. The usual dosage of ticarcillin disodium and clavulanate potassium for the treatment of intra-abdominal infections in adults weighing 60 kg or more is 3.1 g of the 30:1 fixed-ratio combination (3 g of ticarcillin and 100 mg of clavulanic acid) every 4-6 hours.

The duration of therapy depends on the severity of infection; therapy generally should be continued for at least 48 hours after manifestations of infection (e.g., fever, elevated leukocyte count) have subsided. For intra-abdominal infections, therapy is continued for at least 5-7 days, usually for 10-14 days for peritonitis; however, more prolonged therapy may be needed in some cases. If clinical improvement is not evident within 4 days of therapy, or if fever or leukocytosis persists for longer than 5 days, the possibility of undrained intra-abdominal infection or inadequately treated extra-abdominal infection should be considered.

Shorter courses (e.g., 2-5 days) may be appropriate for acute bacterial contamination following penetrating trauma if therapy is initiated soon after injury and surgical measures are instituted promptly. For adults weighing less than 60 kg, the usual dosage of the 30:1 fixed-ratio combination (3 g of ticarcillin and 100 mg of clavulanic acid) is 200-300 mg of ticarcillin per kg daily given in divided doses every 4-6 hours.

Pediatric Dosage

The usual dosage of ticarcillin disodium and clavulanate potassium administered as a 30:1 fixed-ratio combination (3 g of ticarcillin and 100 mg of clavulanic acid) in pediatric patients 3 months to 16 years of age weighing less than 60 kg is 200 mg of ticarcillin per kg daily given in divided doses every 6 hours for the treatment of mild to moderate infections or 300 mg of ticarcillin per kg daily given in divided doses every 4 hours for the treatment of severe infections.

The usual dosage of ticarcillin disodium and clavulanate potassium for the treatment of mild to moderate or severe infections in pediatric patients 3 months to 16 years of age weighing 60 kg or more, is 3.1 g of the 30:1 fixed-ratio combination (3 g of ticarcillin and 100 mg of clavulanic acid) every 6 or 4 hours, respectively.

The American Academy of Pediatrics (AAP) recommends that children beyond the neonatal period receive IM or IV ticarcillin disodium and clavulanate potassium in a dosage of 100-200 mg of ticarcillin per kg daily given in 4 divided doses for the treatment of mild to moderate infections or 200-300 mg of ticarcillin per kg daily given in 4 divided doses for the treatment of severe infections.

Dosage in Renal and Hepatic Impairment

In patients with renal impairment or renal and hepatic impairment, doses and/or frequency of administration of ticarcillin disodium and clavulanate potassium should be modified in response to the degree of impairment. Modification of the usual dosage of ticarcillin disodium and clavulanate potassium is unnecessary in patients with hepatic impairment alone. The manufacturer recommends that adults with impaired renal function receive an initial ticarcillin disodium and clavulanate potassium loading dose of 3.1 g of the 30:1 fixed-ratio combination (3 g of ticarcillin and 100 mg of clavulanic acid) and the following maintenance dosage based on the patient’s creatinine clearance:

Creatinine Clearance (mL/min) Dosage (in terms of Timentin®) 30-60 2 g every 4 h 10-30 2 g every 8 h <10 2 g every 12 h The manufacturer states that adults undergoing hemodialysis should receive an initial ticarcillin disodium and clavulanate potassium loading dose of 3.1 g of the 30:1 fixed-ratio combination followed by a maintenance dosage of 2 g of the drug (in terms of Timentin®) every 12 hours.

An additional 3.1-g dose of the 30:1 fixed-ratio combination should be administered after each dialysis period. In adults undergoing peritoneal dialysis, an initial loading dose of 3.1 g of the 30:1 fixed-ratio combination should be given followed by 3.1 g of the 30:1 fixed-ratio combination every 12 hours. In adults with hepatic dysfunction and a creatinine clearance less than 10 mL/minute, an initial loading ticarcillin disodium and clavulanate potassium dose of 3.1 g of the 30:1 fixed-ratio combination should be given followed by a maintenance dosage of 2 g (in terms of Timentin®) once daily.